Preparation of ethinyl-tetralols



Patented Get. 10, 1950 UNITED STATES OFFICE PREPARATION OF ErHiNYmtrET-RALoLs Mos-es Wolf metal, ripper Montc'lair; and William EdWinScott, Essex Fells, N. J., assignorsto*Hoflniann-La"-Roclie-Inc., Nutle'y, N: J'., a corporation of New Jersey No Drawing. Application December 22,1948, Serial No. 66,852

3 Claims. -(Cl. 260-611) The present invention relates to the synthesis of l-ethinyl-G-lower alkoxy-l-tetralols which can be represented by the following formula:

l CH2 H2 wherein R stands for a lower alkyl group, such as for example, methyl, ethyl, or the like. The compound. where R stands for methyl, has already been described in the literature, whereas the com.- pound where R is ethyl, to the best of our knowledge, is new.

The heretofore described methods for the preparation of the known 1-ethinyl-6-methoxy-l-tetralol are accompanied by many drawbacks, such as low yields, impurities and confinement to small scale operations. According to one of the known methods, G-methoxy-l-tetralone is condensed with acetylene magnesium bromide in the presence of an excess of acetylene under pressure. From the reaction mixture l-ethinyl-fi-methoxyl-tetralol is recoverable in very low yield. Furthermore, it is very dii'hcult to carry out the process in'batches of more than a few grams.

Accordin to another procedure, 6-methoxyl-tetralone is condensed at 40 C. with sodium tion is necessary for further purification of thev 1-ethinyl-6-methoxy-l-tetralol, which is obtained in a yield of not morethan 35 per cent.

By the previously described procedures, the 1-ethinyl-6-methoxy-l-tetralol is obtained in an impure state, and only as an oil.

According to our invention, we have found that l-ethinyl-G-lower alkoxy-l-tetralol's can be readily prepared in high yields and high purity by condensing 6-lower alkoxy-l-tetralones with lithium acetylide in liquid ammonia in the presence of free acetylene, preferably at room temperature. With the new process yields of over 80 per cent of l-ethinyl-B-methoxy-l-tetralol, and of 1-ethinyl-6-ethoxy-l-tetralol, are readily obtainable. The process results in compounds of such purity that they readily crystallize, whereas by the prior procedures, as already stated, the l-ethinyl-6-methoxy-l-tetralolwas obtained only as an oil.

Example 1 grams of G-methoxy-l-tetralone, 7.65 grams of lithium acetylide, and 230 cc. of liquid ammonia were placed in a glass liner for a shaking autoclave. Dry acetylene was passed into the mixture until thevolume had increased by 20 cc. The mixture was then placed in the autoclave, and,

with shaking, allowed to come to room temperature. After shaking 20 hours at room temperature, the autoclave was vented until the pressure dropped, and the liner was then removed. The dark red product was washed from the liner with anhydrous ether.

To the ether-ammonia solution were added slowly 20 grams of ammonium chloride, and the ammonia was distilled off. The residue was treated with ice and water. The ether layer was 1 separated, washedwith water, and dried with anhydrous sodium sulfate. After removal of the ether, the residue was distilled in a vacuum of 0.1 mm. 35 grams of viscous material distilled at 120-131 O. The product was then dissolved in hot ligroin. On cooling an oil separated which readily crystallized. The l-ethinyl-G-methoXy-ltetralol thus obtained had an M. P. 89 C.

Example 2 100 grams of fi-ethoxy-tetralone, 32 grams of lithium acetylide, 1000 cc. of liquid ammonia and In general, the temperature of the reaction may Boiling Grams point, C.

1 Up to 120 0. 64 2 120-122 1. 65 3 122-130 100. 00

Fraction 3 was crystallized from benzol-ligroin, and the crystals of l -ethinyl-S-ethoxy-1-tetralol melted at C; The yield was 87 per cent.

The l-ethinyl-G-lower alkoxy-l-tetralols are useful in the synthesis of steroids.

We claim:

1. A process of preparing l-ethinyl-fi-lower alkoxy-l-tetralol which comprises reacting 6-1ower alkoxy-l-tetralone with lithium acetylide in liquid ammonia in the presence of free acetylene at a temperature between about 15 and about 45 C.

2. A process according to claim 1 in which the 6-1ower alkoxy-l-tetralone is G-methoxy-l-tetralone.

3. A process accordin to claim 1 in which the 6-lower alkoxy-l-tetralone is G-ethoxy-l-tetralone.

MOSES WOLF GOLDBERG. WILLIAM EDWIN SCOTT.

REFERENCES oI'rEi) The following references are of record in the file of this patent:

OTHER REFERENCES Goldberg: Helvetia. Chim. Acta, v01. 23 (1940) pages 836-837.

Dane et a1.: Annalen, vol. 532 (1937) pages 39-51.

Birch: J our. Chem. Soc., London (1944) pages 503-6.

Johnson: Acetylenic Compounds, vol. I, page 13 (1946), publisher, Arnold & Co., London. 

1. A PROCESS OF PREPARING 1-ETHINYL-6-LOWER ALKOXY-1-TETRALOL WHICH COMPRISES REACTING 6-LOWER ALKOXY-1-TETRALONE WITH LITHIUM ACETYHLIDE IN LIQUID AMMONIA IN THE PRESENCE OF FREE ACETYLENE AT A TEMPERATURE BETWEEN ABOUT 15* AND AND 45*C. 